The neutrophil plays a critical role in the pathogenesis of the Adult Respiratory Distress Syndrome (ARDS), as strategies aimed at preventing neutrophil sequestration in the lung, such as neutrophil depletion or administration of antibody directed against adhesion molecules, attenuate lung injury in experimental models. Further, neutrophil-mediated oxidative damage to the alveolocapillary unit is thought to be necessary for the full expression of the syndrome in the majority of cases. The association between oxidative stress and ARDS is suggested by the presence of increases in expired H.sub.2 O.sub.2 .sup.1 as well as an increase in oxidant levels .sup.2 and a reduction in reduced glutathione (GSH) .sup.3 in bronchoalveolar lavage fluid (BALF) obtained from patients with ARDS.
Despite this association, there are relatively few studies demonstrating benefit following administration of exogenous antoxidants in animal models of acute lung injury caused by inflammatory stimuli .sup.4,5, and only one study in man demonstrating marginal efficacy in patients at risk for ARDS .sup.6. These data indicate that oxidant-mediated tissue injury per se may not be the only mechanism whereby the inflammatory process leading to ARDS is initiated. For example, proteases .sup.7 and elastases .sup.8 are released by activated neutrophils and contribute to lung injury, suggesting that greater success at attenuating lung injury may be achieved not only through improving antioxidant defenses, but by limiting cell activation. In this regard, there is accumulating evidence that alterations in the cellular redox state play a critical role in cell signaling through modulation of tyrosine phosphorylation .sup.9, regulation of transcription .sup.10, and alterations in messenger RNA stability .sup.11, suggesting that administration of antioxidants or sulfhydryl-reactive agents may have important modulatory effects on cell activation. GSH is the most abundant intracellular thiol and maintains the intracellular redox state through detoxification of oxidized moieties as a result of the activity of glutathione peroxidase, glutathione S-transferase, and a direct oxidant scavenging effect .sup.12. Several recent studies have demonstrated paradoxical beneficial effects associated with GSH depletion, including improved survival following cerebral ischemia-reperfusion .sup.13, abrogation of hepatic injury following systemic endotoxemia .sup.14, and a reduction in lung injury following the administration of either oxidants or thromboxane in an ex vivo, isolated-perfused model of lung injury .sup.15. The mechanism(s) underlying this protection remains unclear.